Alzheimer's disease and dementia are diseases which result in a progressive deterioration of neurons in the brain. This causes cognitive deterioration and changes in behavior. With dementia and Alzheimer's disease, there is loss of short-term memory and minor forgetfulness which becomes greater as the illness progresses to major memory loss with a relative preservation of older memories. As the disease progresses even further, there is cognitive or intellectual impairment which extends to language degeneration (having difficulty remembering words to being completely unable to speak, read, or write), loss of the ability to execute or carry out learned purposeful movements, and a loss of ability to recognize objects, persons, sounds, shapes, or smells.
Neurons are cells which transmit information via synapses. Neurons connect to each other to form neural networks. Neurons are electrically excitable cells which transmit information by electrical and chemical signaling by synapses which establish connections with other neuron cells. With the progression of dementia, Alzheimer's disease, and other neurodegenerative diseases, the connectivity of the neurons are adversely affected, such as by the generation of plaque and abnormal proteins called tau proteins.
Human olfaction declines with advancing age, with rates of anosmia (loss of sense of smell) approaching 50% of populations 65 and 80 years old, and approximately 75% in those over 80 years. Such diminution in olfaction influences enjoyment of food, nutrition, physical and emotional well-being, quality of life, and safety from fire hazard or from ingestion of contaminated food. Indeed, numerous epidemiologic studies in aging populations now show that olfactory loss predicts dementia, Alzheimer's disease and excess mortality. Therefore, any scientific advances that delay, prevent or reverse age-related olfactory dysfunction, including sense of smell, would have a profound impact at every aspect of our society given the present demographic shift with an exponentially increasing proportion of elderly persons and the growing percentage of those affected by cognitive decline.
The olfactory system (the system which permits humans to sense odors) is one of the most neuroplastic systems in the adult mammal. In the periphery, neurons are continuously generated in the olfactory neuroepithelium and replace older olfactory receptor neurons. These neurons project to the olfactory bulb, another area where neurons are continuously added throughout the life. The primary outputs of the olfactory bulb are to the primary olfactory cortex (POC), which consists of the anterior olfactory nucleus, olfactory tubercle, piriform cortex, periamygdaloid cortex, entorhinal cortex, central amygdaloid nuclei, and nucleus of the lateral olfactory tract. Evidence from neurobiological studies reveals that degenerative changes in these regions underlie age-associated olfactory and cognitive loss. Interestingly, these olfactory regions possess remarkable capacity for activity-dependent neuroplasticity (changes in neural pathways and synapses) in adult mammals.
However, primary neuronal pathways to olfactory regions of the brain generally desensitize within a short period of time. For example, primary neural pathways may desensitize in about one minute. Further, secondary pathways also desensitize within a short period of time, such as in 2-3 minutes. Other pathways may desensitize in shorter or longer periods of time such that the odorants become less efficacious over periods of time. This is especially the case for the intranasal delivery of odorants for the treatment of neurodegenerative diseases where the odorants positively affect olfactory regions of the brain.
Moreover, intranasal administration with positive pressure compared to just breathing room air provides a significant increase in uptake of the odorants and the surprising effect that the odorants have on reversal of symptoms of dementia, Alzheimer's disease and other diseases and traumas. In one form, the inside of human nose is enriched as the odorants exit the cannula and contact olfactory tissue in a positive pressure system as compared to simply breathing room air.